We propose to continue our studies on the mechanisms of alphavirus persistence in mouse L cells and in murine neuroblastoma and glial cells. In particular, we will investigate the nature and extent of viral genomic alterations which accompany persistence and will examine whether these changes are manifest in alterations in the antigenic properties of the virus. Using recombinant DNA technology we will pinpoint these genomic alterations and determine to what extent they are common from cell line to cell line and if they are located in specific regions of the viral RNA. We shall also determine if these alterations result in the evolution of virus with altered virulence both for tissue culture cells and for experimental animals.